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Activated human γδ T cells induce peptide-specific CD8+ T-cell responses to tumor-associated self-antigens

Abstract

Specific cellular immunotherapy of cancer requires efficient generation and expansion of cytotoxic T lymphocytes (CTLs) that recognize tumor-associated self-antigens. Here, we investigated the capacity of human γδ T cells to induce expansion of CD8+ T cells specific for peptides derived from the weakly immunogenic tumor-associated self-antigens PRAME and STEAP1. Coincubation of aminobisphosphonate-stimulated human peripheral blood-derived γδ T cells (Vγ9+Vδ2+), loaded with HLA-A*02-restricted epitopes of PRAME, with autologous peripheral blood CD8+ T cells stimulated the expansion of peptide-specific cytolytic effector memory T cells. Moreover, peptide-loaded γδ T cells efficiently primed antigen-naive CD45RA+ CD8+ T cells against PRAME peptides. Direct comparisons with mature DCs revealed equal potency of γδ T cells and DCs in inducing primary T-cell responses and peptide-specific T-cell activation and expansion. Antigen presentation by γδ T-APCs was not able to overcome the limited capacity of peptide-specific T cells to interact with targets expressing full-length antigen. Importantly, T cells with regulatory phenotype (CD4+CD25hiFoxP3+) were lower in cocultures with γδ T cells compared to DCs. In summary, bisphosphonate-activated γδ T cells permit generation of CTLs specific for weakly immunogenic tumor-associated epitopes. Exploiting this strategy for effective immunotherapy of cancer requires strategies that enhance the avidity of CTL responses to allow for efficient targeting of cancer.

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Acknowledgments

This work was supported by a grant from the Deutsche Krebshilfe (to C. R.) and by a grant from the Wilhelm-Sander-Stiftung (to C.R.).

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The authors declare that they have no conflict of interest.

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Correspondence to Claudia Rossig.

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Altvater, B., Pscherer, S., Landmeier, S. et al. Activated human γδ T cells induce peptide-specific CD8+ T-cell responses to tumor-associated self-antigens. Cancer Immunol Immunother 61, 385–396 (2012). https://doi.org/10.1007/s00262-011-1111-6

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  • DOI: https://doi.org/10.1007/s00262-011-1111-6

Keywords

  • Antigen presentation
  • γδ T cells
  • Tumor antigens
  • Self-antigens
  • Cellular therapy